A sedentary lifestyle is a major risk factor for cardiovascular disease, the leading cause of death in the United States. Cardiovascular diseases related to physical inactivity are associated with overactivity of the sympathetic nervous system. The long term goal of the applicant is to understand the mechanisms by which a sedentary lifestyle contributes to the increased incidence of cardiovascular disease. The objective of the current proposal is to test the hypothesis that physical inactivity versus physical activity produces differential alterations in the structure and function of a specific population of neurons in the brainstem that are critical for blood pressure regulation. In order to achieve the objectives of this proposal, the PI has assembled an expert team at the University of Missouri and the Flinders Institute in Australia. We expect to establish at the end of this two year project the extent to which physical activity and inactivity regulates the structure and function of spinally projecting neurons in the rostral ventrolateral medulla. Strong preliminary data and previously published data support these provocative and unique hypotheses. The results of this proposal will provide a greater understanding of the detrimental effects of a sedentary lifestyle on cardiovascular health and define potential therapeutic targets for the treatment and prevention of cardiovascular diseases. [unreadable] [unreadable] [unreadable]